We study the biology of somatic gene transfer, and aim to use the knowledge and the technologies that emerge from this research toward improving and accelerating the field of gene therapy. Durable and efficient gene transfer is often best accomplished through the use of viral vectors. We therefore study the biology and host interactions of a number of viruses in order to evaluate and improve their function as a vector. Viruses of study are retro- and lentivirus, adenovirus, and the adeno-associated virus (AAV). Clinically, we build toward gene therapies of inherited forms of blindness, as the retina has many features that make it a good substrate to move these experimental therapies forward.

Specifically, we study viral evolution on a structural and molecular level to learn more about host-virus and host-vector interactions, and ultimately to improve the design of viral vectors for clinical use. Immunity raised against the wild type virus and vector are directly relevant to gene therapy applications as they affect the safety and efficacy of the treatment. We hypothesize that AAV has evolved primarily under pressures of the host immune system, and aim at understanding how the virus has effectively been able to avoid immunity throughout its natural history. In order to do so, the virus deploys molecular immune escape mechanisms, mutates to alter its antigenic profile, and evolves functionally. In doing so, it is tasked to maintain structural integrity and core functions that enable it to infect cells and successfully complete its life cycle. We are therefore interested in the structural biology of AAV, the simplest and smallest of mammalian viruses, and aim to understand the mechanism of virus transduction and particle formation.